The major objective of this proposal is to obtain information which will provide insight into the pathogenesis and significance of capillary basement membrane thickening per se, and its relevance to the pathogenesis of cardiovascular disease in general and to the microangiopathies of diabetes mellitus in particular. Quantitative electron microscopic techniques will be used to assess basement membrane width of muscle capillaries obtained by needle biopsy of quadriceps femoris muscle. This data will be correlated with metabolic studies and hormonal assays of insulin, growth hormone, and glucagon. In vitro studies of isolated glomeruli from rat kidney will be performed to assess the influence of various hormonal excesses and deficiencies on basement membrane synthesis.